Modulation of calcium concentrations within the cardiac cell plays a key role in determining the contractile force of the heart. Intracellular calcium available for delivery to the contractile proteins is derived partly from calcium entering the cell from the extracellular compartment, and, more directly, from intracellular stores such as the sarcoplasmic reticulum. Cyclic AMP-dependent protein kinase catalyzes the phosphorylation of a 22,000 molecular weight protein that has been shown to increase calcium transport across the membranes of the sarcoplasmic reticulum. The aim of the proposed study is to purify the 22,000 molecular protein and to define its regulatory interaction with the Ca-transport system of the heart's sarcoplasmic reticulum. The distribution of this phosphoprotein in other cardiac cell organelles and in other tissues will be examined. These studies should provide basic new information on the regulation of myocardial contractility by inotropic agents, such as epinephrine, which activate adenylate cyclase.